Currently, there are various delivery systems for the topical application of pharmaceutical compounds, for example, lotions, creams, gels, ointments, transdermal patches, and sprays. Typically, the selection of a delivery system depends upon the desired pharmacokinetic profile of the specific therapeutic agent, for example, whether immediate, short-term, or sustained release is required for the administration of the therapeutic agent. Occlusion problems are common with many of the systems, and they may also cause skin irritation. Many pharmaceutical compounds, for example, hormonal drugs, are conveniently delivered using a transdermal patch. Typically, the patch is comprised of an occlusive vacuum membrane, which often results in a local skin irritation. In addition, with transdermal patches, the penetration of the drug into the skin is often poor. With reference to conventional topical spray formulations, the therapeutic agent tends to remain at the application site for only a short period of time and can be easily rubbed off or made unavailable for penetration into the skin.
The preparation of controlled drug delivery systems for topical application is often more of an art than a science. Many factors directly affect the release rate of a therapeutic agent, and oftentimes, the correct formulation for efficient delivery of a therapeutic agent is found by trial and error.
Controlled release of topic drug delivery occurs when a polymer is measurably combined with an active agent or therapeutically active agent in such a way that the active agent is released from the polymer at a controlled rate. The release of the active agent may be constant over a period of time, may be cyclic, or may commence by environmental or other external events.
There are three known primary mechanisms by which an active agent can be released from a delivery system: (a) diffusion, (b) degradation, and (c) swelling followed by diffusion. Any or all of the foregoing mechanisms may occur in one release system.
Diffusion occurs when a drug or other active agent passes through the polymer that forms the controlled release device. The diffusion can occur on a macroscopic scale as through pores in the polymer matrix—or on a molecular level by passing between polymer chains or through microchannels placed in the polymer matrix.
Controlled-release topical delivery systems can be designed so that the system will not release its agent until it is placed in the appropriate biological and environmental conditions. For example, controlled-release systems are initially dry. When placed over the body on the skin, the controlled-release system absorbs water or fluid from the skin (or other body fluids) and will increase in size. The swelling increases the aqueous solvent content within the formulation as well as the polymer mesh size, enabling the therapeutic agent to diffuse through the swollen network into the external environment.
U.S. Pat. No. 2,352,508 discloses a wound dressing comprising a net substrate encapsulated in hydrophilic tacky resin coating leaving the apertures in the net substrate unoccluded. The coating is a polyurethane that may contain active agents such as sulphadiazine, wherein the coated substrate is laminated between two release liners.
U.S. Pat. No. 6,326,410 describes a wound contact layer formed from a polyurethane foam. The foam may deliver active agents.
U.S. Published Application 2002/0128578 describes a medical device comprising multiple sheets having microchannels useful for wound dressing and drug delivery. The articles comprise layers having microchannels that are made of polyurethane or polyvinylacetate to facilitate the delivery of pharmaceutical compounds.
U.S. Pat. No. 6,183,770 describes a patch for delivery of active agents locally to the skin in a manner to minimize the adverse effects of adhesives on active agents.
U.S. Pat. No. 6,352,715 describes a transdermal drug delivery system whereby huperzine, a naturally occurring acetylcholine esterase inhibitor, is administered for the treatment of Alzheimer's Disease. The transdermal delivery device is a patch.
U.S. Pat. No. 7,045,145 describes a transdermal contraceptive delivery system for fertility control in women when synthetic estrogen, ethanol estrodiol and synthetic progestin are dispersed through a patch comprising a backing layer, and an adjoining layer of a solid absorption adhesive.
U.S. Pat. No. 5,919,476 describes a bandage in the form of a reinforced silicone gel sheet for application to scar tissue. The bandage comprises three layers; a tacky skin contacting first layer made from a silicone sheet, a reinforcing second layer comprising a non-liquid permeable mesh fabric support structure having a plurality of holes there-through and a non-tacky bonding third layer which includes the holes and laminates itself to the first layer, thereby securing the second layer between the first and third layer.
U.S. Pat. No. 5,895,656 describes a gas or gel filled silicone bandage made of silicone sheeting for treating wounds and scar tissue. The flexible silicone sheeting or film contains an interior space that may be filled with dry gas or a hydrophobic gel. Since there is reduced electrical resistance in scar tissue, the use of the hollow space in the bandage may increase the static electrical field or negative charge applied to the scar which could hasten the inhibitatory healing process for hypertrophic and keloid scars. To improve the electric field within the hollow space, small pieces of Teflon™ sheeting or silicone beads may be inserted in the hollow space.
U.S. Pat. No. 5,759,560 describes a silicone thermal plastic sheeting for scar treatment which has two layers, a first layer of a therapeutic agent to be placed on to the skin and a second backing layer of a thermoplastic polymer bonded to the first layer to provide a thick shape to the material.